Meta-analysis of Risk Reduction Estimates Associated With Risk-Reducing Salpingo-Oophorectomy in BRCA1 or BRCA2 Mutation Carriers

Timothy R. Rebbeck; Noah D. Kauff; Susan M. Domchek

Disclosures

J Natl Cancer Inst. 2009;101(2):80-87. 

In This Article

Results

The studies that formed the basis of this meta-analysis included case-control studies as well as prospective and retrospective cohort studies ( Table 1 ). As can be seen in this summary, limitations of the currently available data regarding RRSO in BRCA1/2 mutation carriers include variable study designs, small sample sizes for individual studies, many of which are retrospective in nature, and short post-RRSO follow-up times in prospective studies. Eight studies[8,9,10,12,13,14,15,16] estimated the risk of breast cancer in BRCA1/2 mutation carriers who were treated with RRSO relative to BRCA1/2 mutation carriers who did not receive this treatment ( Table 2 ). As summarized in Table 3 and Figure 1, three nonoverlapping studies,[14,15,16] which included 5703 participants, estimated the risk of breast cancer in BRCA1/2 mutation carriers who received RRSO relative to BRCA1/2 mutation carriers who did not receive the procedure, giving a summary HR estimate of 0.49 (95% CI = 0.37 to 0.65). Four nonoverlapping studies[12,14,15,16] estimated the risk reduction associated with RRSO for breast cancer in BRCA1 mutation carriers, giving a summary HR estimate of 0.47 (95% CI = 0.35 to 0.64). Finally, three nonoverlapping studies[14,15,16] estimated the relative risk for breast cancer in BRCA2 mutation carriers, giving a summary HR estimate of 0.47 (95% CI = 0.26 to 0.84) ( Table 3 , Figure 1).

Forest plots of relative risk (RR) estimates for risk reduction associated with risk-reducing salpingo-oophorectomy (RRSO). A) Ovarian cancer risk reduction in BRCA1/2 mutation carriers. B) Breast cancer risk reduction in BRCA1/2 mutation carriers. C) Breast cancer risk reduction in BRCA1 mutation carriers. D) Breast cancer risk reduction in BRCA2 mutation carriers. The box sizes reflect the relative sample sizes of the individual studies; horizontal lines represent 95% confidence intervals (CIs). Diamonds represent the pooled point estimate and 95% confidence intervals. Vertical dashed lines represent the pooled relative risk estimate. Estimates less than a value of 1.0 suggest a favorable reduction in cancer risk associated with RRSO.

Six studies[8,10,11,13,16,17] ( Table 2 ) estimated the risk of gynecologic cancer in BRCA1/2 mutation carriers treated with RRSO relative to BRCA1/2 mutation carriers who did not receive this treatment. Based on data from the three nonoverlapping datasets,[11,16,17] which included 2840 participants, the summary HR was 0.21 (95% CI = 0.12 to 0.39) ( Table 3 , Figure 1). Only one study[16] estimated the risk of gynecologic cancer in BRCA1 mutation carriers treated with RRSO relative to untreated BRCA1 carriers (HR = 0.15, 95% CI = 0.04 to 0.56) ( Table 2 ). No study estimated the risk reduction associated with RRSO in BRCA2 mutation carriers. Kauff et al.[16] did investigate risk reduction in 294 women with BRCA2 mutations, but observed no post-RRSO gynecologic cancers in this sample.

We found no evidence of publication bias of any of our estimates based on the Begg and Majumder test statistics presented in Table 3 . No evidence of study heterogeneity was found based on the x 2 test ( Table 3 ).

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